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K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates.

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Title: K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates.
Authors: Straimer, Judith, Gnädig, Nina F., Witkowski, Benoit, Amaratunga, Chanaki, Duru, Valentine, Ramadani, Arba Pramundita, Dacheux, Mélanie, Khim, Nimol, Lei Zhang, Lam, Stephen, Gregory, Philip D., Urnov, Fyodor D., Mercereau-Puijalon, Odile, Benoit-Vical, Françoise, Fairhurst, Rick M., Ménard, Didier, Fidock, David A.
Source: Science (pre-March 2025). 1/23/2015, Vol. 347 Issue 6220, p428-431. 4p.
Subjects: Plasmodium falciparum genetics, Genetic mutation, Transgenic organisms, Artemisinin, Drug resistance in microorganisms, Malaria treatment, Malaria prevention, International cooperation, Therapeutics
Geographic Terms: Southeast Asia
Abstract: The emergence of artemisinin resistance in Southeast Asia imperils efforts to reduce the global malaria burden. We genetically modified the locus Plasmodium falciparum K13 using zinc-finger nucleases and measured ring-stage survival rates after drug exposure in vitro; these rates correlate with parasite clearance half-lives in artemisinin-treated patients. With isolates from Cambodia, where resistance first emerged, survival rates decreased from 13 to 49% to 0.3 to 2.4% after the removal of K13 mutations. Conversely, survival rates in wild-type parasites increased from ≤0.6% to 2 to 29% after the insertion of K13 mutations. These mutations conferred elevated resistance to recent Cambodian isolates compared with that of reference lines, suggesting a contemporary contribution of additional genetic factors. Our data provide a conclusive rationale for worldwide K13-propeller sequencing to identify and eliminate artemisinin-resistant parasites. [ABSTRACT FROM AUTHOR]
Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
Database: Psychology and Behavioral Sciences Collection
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  Data: K13-propeller mutations confer artemisinin resistance in Plasmodium falciparum clinical isolates.
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  Data: <searchLink fieldCode="AR" term="%22Straimer%2C+Judith%22">Straimer, Judith</searchLink><br /><searchLink fieldCode="AR" term="%22Gnädig%2C+Nina+F%2E%22">Gnädig, Nina F.</searchLink><br /><searchLink fieldCode="AR" term="%22Witkowski%2C+Benoit%22">Witkowski, Benoit</searchLink><br /><searchLink fieldCode="AR" term="%22Amaratunga%2C+Chanaki%22">Amaratunga, Chanaki</searchLink><br /><searchLink fieldCode="AR" term="%22Duru%2C+Valentine%22">Duru, Valentine</searchLink><br /><searchLink fieldCode="AR" term="%22Ramadani%2C+Arba+Pramundita%22">Ramadani, Arba Pramundita</searchLink><br /><searchLink fieldCode="AR" term="%22Dacheux%2C+Mélanie%22">Dacheux, Mélanie</searchLink><br /><searchLink fieldCode="AR" term="%22Khim%2C+Nimol%22">Khim, Nimol</searchLink><br /><searchLink fieldCode="AR" term="%22Lei+Zhang%22">Lei Zhang</searchLink><br /><searchLink fieldCode="AR" term="%22Lam%2C+Stephen%22">Lam, Stephen</searchLink><br /><searchLink fieldCode="AR" term="%22Gregory%2C+Philip+D%2E%22">Gregory, Philip D.</searchLink><br /><searchLink fieldCode="AR" term="%22Urnov%2C+Fyodor+D%2E%22">Urnov, Fyodor D.</searchLink><br /><searchLink fieldCode="AR" term="%22Mercereau-Puijalon%2C+Odile%22">Mercereau-Puijalon, Odile</searchLink><br /><searchLink fieldCode="AR" term="%22Benoit-Vical%2C+Françoise%22">Benoit-Vical, Françoise</searchLink><br /><searchLink fieldCode="AR" term="%22Fairhurst%2C+Rick+M%2E%22">Fairhurst, Rick M.</searchLink><br /><searchLink fieldCode="AR" term="%22Ménard%2C+Didier%22">Ménard, Didier</searchLink><br /><searchLink fieldCode="AR" term="%22Fidock%2C+David+A%2E%22">Fidock, David A.</searchLink>
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  Data: <searchLink fieldCode="JN" term="%22Science+%28pre-March+2025%29%22">Science (pre-March 2025)</searchLink>. 1/23/2015, Vol. 347 Issue 6220, p428-431. 4p.
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  Data: <searchLink fieldCode="DE" term="%22Plasmodium+falciparum+genetics%22">Plasmodium falciparum genetics</searchLink><br /><searchLink fieldCode="DE" term="%22Genetic+mutation%22">Genetic mutation</searchLink><br /><searchLink fieldCode="DE" term="%22Transgenic+organisms%22">Transgenic organisms</searchLink><br /><searchLink fieldCode="DE" term="%22Artemisinin%22">Artemisinin</searchLink><br /><searchLink fieldCode="DE" term="%22Drug+resistance+in+microorganisms%22">Drug resistance in microorganisms</searchLink><br /><searchLink fieldCode="DE" term="%22Malaria+treatment%22">Malaria treatment</searchLink><br /><searchLink fieldCode="DE" term="%22Malaria+prevention%22">Malaria prevention</searchLink><br /><searchLink fieldCode="DE" term="%22International+cooperation%22">International cooperation</searchLink><br /><searchLink fieldCode="DE" term="%22Therapeutics%22">Therapeutics</searchLink>
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– Name: Abstract
  Label: Abstract
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  Data: The emergence of artemisinin resistance in Southeast Asia imperils efforts to reduce the global malaria burden. We genetically modified the locus Plasmodium falciparum K13 using zinc-finger nucleases and measured ring-stage survival rates after drug exposure in vitro; these rates correlate with parasite clearance half-lives in artemisinin-treated patients. With isolates from Cambodia, where resistance first emerged, survival rates decreased from 13 to 49% to 0.3 to 2.4% after the removal of K13 mutations. Conversely, survival rates in wild-type parasites increased from ≤0.6% to 2 to 29% after the insertion of K13 mutations. These mutations conferred elevated resistance to recent Cambodian isolates compared with that of reference lines, suggesting a contemporary contribution of additional genetic factors. Our data provide a conclusive rationale for worldwide K13-propeller sequencing to identify and eliminate artemisinin-resistant parasites. [ABSTRACT FROM AUTHOR]
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  Data: <i>Copyright of Science (pre-March 2025) is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites without the copyright holder's express written permission. Additionally, content may not be used with any artificial intelligence tools or machine learning technologies. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract.</i> (Copyright applies to all Abstracts.)
PLink https://search.ebscohost.com/login.aspx?direct=true&site=eds-live&db=pbh&AN=100585214
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        Value: 10.1126/science.1260867
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        Text: English
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      – SubjectFull: Artemisinin
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